Hepatic encephalopathy

Suggested reading

Here is a selection of the most up-to-date publications about developments in liver disease and hepatic encephalopathy:

  • Wang DW, Yin YM, Yao YM. Advances in the management of acute liver failure. World J Gastroenterol. 2013;19(41):7069-7077.
  • Loo NM, Souza FF, Garcia-Tsao G. Non-hemorrhagic acute complications associated with cirrhosis and portal hypertension. Best Pract Res Clin Gastroenterol. 2013;27(5):665-78.
  • Prakash RK, Kanna S, Mullen KD. Evolving concepts: the negative effect of minimal hepatic encephalopathy and role for prophylaxis in patients with cirrhosis. Clin Ther. 2013;35(9):1458-73.
  • Chacko KR, Sigal SH. Update on management of patients with overt hepatic encephalopathy. Hosp Pract (1995). 2013;41(3):48-59.
  • Keiding S, Pavese N. Brain metabolism in patients with hepatic encephalopathy studied by PET and MR. Arch Biochem Biophys. 2013;536(2):131-42.
  • Sergeeva OA. GABAergic transmission in hepatic encephalopathy. Arch Biochem Biophys. 2013;536(2):122-30.
  • Butz M, May ES, Häussinger D, Schnitzler A. The slowed brain: cortical oscillatory activity in hepatic encephalopathy. Arch Biochem Biophys. 2013;536(2):197-203.
  • Coltart I, Tranah TH, Shawcross DL. Inflammation and hepatic encephalopathy. Arch Biochem Biophys. 2013;536(2):189-96.
  • Kappus MR, Leszczyszyn DJ, Moses L, et al. Effect of obstructive sleep apnea on the sleep architecture in cirrhosis. J Clin Sleep Med. 2013;9(3):247-51.
  • Palomero-Gallagher N, Zilles K. Neurotransmitter receptor alterations in hepatic encephalopathy: a review. Arch Biochem Biophys. 2013;536(2):109-21.
  • Rahimi RS, Rockey DC. End-stage liver disease complications. Curr Opin Gastroenterol. 2013;29(3):257-63.
  • Yu C, Sharma N, Saab S. Hyponatremia: clinical associations, prognosis, and treatment in cirrhosis. Exp Clin Transplant. 2013;11(1):3-11.
  • Cichoż-Lach H, Michalak A. Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. World J Gastroenterol. 2013;19(1):26-34.
  • Tranah TH, Vijay GK, Ryan JM, Shawcross DL. Systemic inflammation and ammonia in hepatic encephalopathy. Metab Brain Dis. 2013;28(1):1-5.
  • Poh Z, Chang PE. A current review of the diagnostic and treatment strategies of hepatic encephalopathy. Int J Hepatol. 2012;2012:480309.
  • Bleibel W, Al-Osaimi AM. Hepatic encephalopathy. Saudi J Gastroenterol. 2012;18(5):301-9.
  • Zhang LJ, Zheng G, Zhang L, et al. Altered brain functional connectivity in patients with cirrhosis and minimal hepatic encephalopathy: a functional MR imaging study. Radiology. 2012;265(2):528-36.
  • Rose CF. Ammonia-lowering strategies for the treatment of hepatic encephalopathy. Clin Pharmacol Ther. 2012;92(3):321-31.
  • Kircheis G, Häussinger D. [Hepatic encephalopathy]. Dtsch Med Wochenschr. 2012;137(31-32):1582-5.
  • Kappus MR, Bajaj JS. Covert hepatic encephalopathy: not as minimal as you might think. Clin Gastroenterol Hepatol. 2012;10(11):1208-19.

Hepa-Merz® – Summary of prescribing information

Hepa-Merz® Granules. Composition: One sachet with 5 g of Granules contains: Active substance: 3 g L-ornithine- L-aspartate. Excipients: citric acid, aspartame (E951), povidone 25, fructose, flavorings, orange yellow S (E110). Note for diabetics: One sachet of Hepa-Merz® Granules contains 1.13 g of fructose (corresponds to approx. 0.11 BU). Therapeutic indications: Treatment of concomitant disease and sequelae due to impaired detoxification activity (e.g. in cirrhosis of the liver) with the symptoms of latent and manifest hepatic encephalopathy. Contraindications: Absolute: Hypersensitivity to L-ornithine-L-aspartate, orange yellow S or any of the other excipients. Severely impaired renal function (renal insufficiency). A serum creatinine value over 3 mg/100 ml can be used as a guideline value. Relative: Pregnancy and lactation: No clinical data are available relating to intake of Hepa-Merz® Granules in children and during pregnancy. No exhaustive animal studies have been performed for L-ornithine-L-aspartate, to investigate its toxicity in relation to reproduction. Administration of Hepa-Merz® Granules during pregnancy should therefore be avoided. If, however, treatment with Hepa-Merz® Granules is considered necessary, careful consideration should be given to the benefit versus risk ratio. It is not known whether L-ornithine-L-aspartate is excreted into the breast milk. Administration of Hepa-Merz® Granules should therefore be avoided during lactation. If, however, treatment with Hepa-Merz® Granules is considered necessary, careful consideration should be given to the benefit versus risk ratio. No data regarding fertility. Undesirable effects: Uncommon (³ 1/1,000 to < 1/100): Nausea, vomiting, stomach ache, flatulence, diarrhea. Very rare (< 1/10,000): Pain in the limbs. These undesirable effects are usually transient and do not require withdrawal of the medicine. Orange yellow S (E110) can trigger allergic reactions. Warnings: Hepa-Merz® Granules contain fructose. Patients with rare hereditary problems of fructose intolerance should not take this medicine. Aspartame (E951): Contains a source of phenylalanine. May be harmful for people with phenylketonuria. Further precautions: As a result of the disease, the ability to drive and operate machinery may be impaired during treatment with L-ornithine-L-aspartate.

Hepa-Merz® Granules. Composition: One sachet with 5 g of Granules contains: Active substance: 3 g L-ornithine- L-aspartate. Excipients: citric acid, saccharin sodium, sodium cyclamate, povidone 25, fructose, flavorings, orange yellow S (E110). Note for diabetics: One sachet of Hepa-Merz® Granules contains 1.13 g of fructose (corresponds to approx. 0.11 BU). Therapeutic indications: Treatment of concomitant disease and sequelae due to impaired detoxification activity (e.g. in cirrhosis of the liver) with the symptoms of latent and manifest hepatic encephalopathy. Contraindications: Absolute: Hypersensitivity to L-ornithine-L-aspartate, orange yellow S or any of the other excipients. Severely impaired renal function (renal insufficiency). A serum creatinine value over 3 mg/100 ml can be used as a guideline value. Relative: Pregnancy and lactation: No clinical data are available relating to intake of Hepa-Merz® Granules in children and during pregnancy. No exhaustive animal studies have been performed for L-ornithine-L-aspartate, to investigate its toxicity in relation to reproduction. Administration of Hepa-Merz® Granules during pregnancy should therefore be avoided. If, however, treatment with Hepa-Merz® Granules is considered necessary, careful consideration should be given to the benefit versus risk ratio. It is not known whether L-ornithine-L-aspartate is excreted into the breast milk. Administration of Hepa-Merz® Granules should therefore be avoided during lactation. If, however, treatment with Hepa-Merz® Granules is considered necessary, careful consideration should be given to the benefit versus risk ratio. No data regarding fertility. Undesirable effects: Uncommon (³ 1/1,000 to < 1/100): Nausea, vomiting, stomach ache, flatulence, diarrhea. Very rare (< 1/10,000): Pain in the limbs. These undesirable effects are usually transient and do not require withdrawal of the medicine. Orange yellow S (E110) can trigger allergic reactions. Warnings : Hepa-Merz® Granules contain fructose. Patients with rare hereditary problems of fructose intolerance should not take this medicine. Further precautions: As a result of the disease, the ability to drive and operate machinery may be impaired during treatment with L-ornithine-L-aspartate.

Hepa-Merz® Infusion concentrate. Composition: One ampoule of 10 ml contains: Active substance: 5 g L-ornithine-L-aspartate. Excipients: Water for injections. Therapeutic indications: Latent and manifest hepatic encephalopathy. Contraindications: Absolute: Hypersensitivity to L-ornithine-L-aspartate. Severe renal impairment (renal failure). A serum creatinine level in excess of 3 mg/100 ml can be taken as a guide. Relative: Pregnancy and lactation: There are no clinical data available on the use of Hepa-Merz® Infusion concentrate in children and during pregnancy. L-ornithine L-aspartate has been investigated for reproduction toxicity only to a limited extent in experimental animal studies. The administration of Hepa-Merz® Infusion concentrate in pregnancy should therefore be avoided. If treatment with Hepa-Merz® is nevertheless thought to be necessary, the benefits and risks should be carefully assessed. It is not known whether L-ornithine-L-aspartate passes into breast milk. Administration of Hepa-Merz® should therefore be avoided during lactation. If treatment with Hepa-Merz® is nevertheless thought to be necessary, the benefits and risks should be carefully assessed. No data regarding fertility. Undesirable effects: Uncommon (³ 1/1,000 to < 1/100): Nausea. Rare (³ 1/10,000 to < 1/1,000): vomiting. Frequency not known (frequency cannot be estimated from the available data): hypersensitivity, anaphylactic reaction. Generally however, the gastrointestinal symptoms are transient, and do not necessitate discontinuation of treatment. They disappear on reduction of the dose or the infusion rate. Further precautions: Hepa-Merz concentrate for solution for infusion can be mixed with the usual infusion solutions. So far, no peculiarities have been observed with regard to miscibility. However, the ampoules should be admixed to the infusion solution only immediately before application. At high doses of Hepa-Merz® Infusion concentrate, serum and urine urea levels should be monitored. If liver function is substantially impaired, the infusion rate must be adjusted to the individual patient in order to prevent nausea and vomiting. Depending on the underlying disease, the ability to drive and operate machines may also be impaired on treatment with L-ornithine L-aspartate. Hepa-Merz® Infusion concentrate must not be injected into an artery. Status: January 2016. Merz Pharmaceuticals GmbH, 60048 Frankfurt.